Giuseppe
Emeritus
Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein. (J Virol., abstract, edited)
[Source: US National Library of Medicine, LINK. EDITED.]
J Virol. 2010 Mar 10. [Epub ahead of print]
Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein.
Versteeg GA, Hale BG, van Boheemen S, Wolff T, Lenschow DJ, Garc?a-Sastre A. - Department of Microbiology, Department of Medicine, Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place,New York, NY 10029, USA; Robert Koch-Institute, FG17, 13353 Berlin, Germany; Department of Internal Medicine, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses. Here, we established complete E1-activating, E2-conjugating, and E3-ligase dependent expression systems for assaying both human and mouse ISGylation. We confirm that human HerC5, but not human HerC6, has ISG15 E3 ligase activity, and identify mouse HerC6 as a bonafide ISG15 E3 ligase. Furthermore, we demonstrate that influenza B virus NS1 protein potently antagonizes human, but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human, but not mouse, ISG15. Using chimeric human/mouse ISG15 constructs we show that the B/NS1:ISG15 interaction is both necessary and sufficient to inhibit ISGylation regardless of the ligation machinery used. Inability to block ISGylation in certain species may contribute to limiting influenza B virus host-range.
PMID: 20219937 [PubMed - as supplied by publisher]
J Virol. 2010 Mar 10. [Epub ahead of print]
Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein.
Versteeg GA, Hale BG, van Boheemen S, Wolff T, Lenschow DJ, Garc?a-Sastre A. - Department of Microbiology, Department of Medicine, Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place,New York, NY 10029, USA; Robert Koch-Institute, FG17, 13353 Berlin, Germany; Department of Internal Medicine, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses. Here, we established complete E1-activating, E2-conjugating, and E3-ligase dependent expression systems for assaying both human and mouse ISGylation. We confirm that human HerC5, but not human HerC6, has ISG15 E3 ligase activity, and identify mouse HerC6 as a bonafide ISG15 E3 ligase. Furthermore, we demonstrate that influenza B virus NS1 protein potently antagonizes human, but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human, but not mouse, ISG15. Using chimeric human/mouse ISG15 constructs we show that the B/NS1:ISG15 interaction is both necessary and sufficient to inhibit ISGylation regardless of the ligation machinery used. Inability to block ISGylation in certain species may contribute to limiting influenza B virus host-range.
PMID: 20219937 [PubMed - as supplied by publisher]